GR-MD-02 + Pembrolizumab Versus Pembrolizumab Monotherapy in Melanoma and Squamous Cell Head and Neck Cancer Patients

Inclusion Criteria: * Patients with unresectable or metastatic melanoma including unknown primary, mucosal or uveal melanomas. Histological confirmation of melanoma will be required by previous biopsy or cytology. Patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression during or after platinum-containing chemotherapy are eligible. PD-L1 testing is not needed for OHN cancers. * Patients who have received anti-PD1 or anti-PD-L1 in the past are eligible if it has been at least 6 months since the last anti-PD-1 or PD-L1 dose, they meet all other eligibility criteria and progression of malignancy has been documented on imaging. Progression for this patient subset is defined as the appearance of one or more new metastatic sites, or a 5% or greater increase in the sum of diameter of target lesions or an unequivocal increase in non-target site. Treatment naïve melanoma patients are eligible. * Patients must be ≥ 18 years of age. * ECOG performance status of 0-2. * Women of childbearing potential must have a serum or urine pregnancy test performed within 72 hours prior to the start of protocol treatment. The results of this test must be negative in order for the patient to be eligible. In addition, women of childbearing potential as well as male patients must agree to take appropriate precautions to avoid pregnancy. * No active bleeding. * Anticipated lifespan greater than 12 weeks. * Patients must sign a study-specific consent document. Exclusion Criteria: * Patients who have previously received a galectin antagonist. * Patients with active autoimmune disease except for autoimmune thyroiditis or vitiligo (see Appendix C). * Patients with history of autoimmune colitis. * Patients with untreated brain metastases. Patients with treated brain metastases who demonstrate control of brain metastases with follow-up imaging 4 or more weeks after initial therapy are eligible. * Patients requiring other systemic oncologic therapy, including experimental therapies. * Patients with active infection requiring antibiotics. * Pregnant or lactating women, as treatment involves unforeseeable risks to the embryo or fetus. * Need for steroids at greater than physiologic replacement doses. Inhaled corticosteroids are acceptable. * Laboratory exclusions (to be performed within 28 days of enrollment): * WBC \< 3.0 x 109/L * Hgb \< 9.0 g/dL * AST or ALT \> 1.5 times ULN * Total bilirubin \> 1.9 g/dL, unless due to Gilbert's Syndrome. If Gilbert's Syndrome is present by clinical history, then direct bilirubin must by \< 3.0 g/dl. * Known history of HIV * Known history of Hepatitis B * Known history of Hepatitis C * INR \> 1.5x ULN * Inability to give informed consent and comply with the protocol. Patients must be judged able to understand fully the investigational nature of the study and the risks associated with the therapy. * Any medical condition that in the opinion of the Principal Investigator would compromise the safety or conduct of the study procedures. * Unresolved immune-mediated pneumonitis, diarrhea, elevation of hepatocellular enzymes or other toxicities requiring greater than physiological replacement doses of steroids.